Patients' recovery and non-recovery narratives after intravenous ketamine for treatment-resistant depression

Background: Intravenous (IV) ketamine is an effective therapy for treatment-resistant depression. A large data base is confirmatory and steadily expanding. Qualitative studies can inform best practices and suggest new research directions. As part of a clinical trial designed to identify biomarkers of ketamine response, a qualitative study was conducted to characterize experiences with: receiving infusions; recovering or not recovering from depression; and beliefs about why ketamine worked or did not work.

Methods: Adults with treatment-resistant depression received three IV ketamine infusions in a two-week period and were characterized as remitters or non-remitters via symptom reduction 24 h after the third infusion. Qualitative interviews of a subset of participants were audio recorded, transcribed verbatim, and coded using deductive and inductive methods. Themes were derived and compared across a broader construct of recovery status.

Results: Of the 21 participants, nine (43 %) were characterized as having experienced remission and 12 (57 %) non-remission. Of the 12 non-remitters, five were characterized as having experienced partial recovery based on their subjective experiences, reporting substantial benefit from ketamine infusions despite non-remission status based on scale measurements. Attributions for ketamine's effects included biological and experiential mechanisms. Among non-remitters there was risk of disappointment when adding another failed treatment.

Limitations: A more diverse sample may have yielded different themes. Different patients had different amounts of time elapsed between ketamine infusions and qualitative interview.

Conclusions: Qualitative methods may enhance researchers' characterization of IV ketamine's impact on treatment-resistant depression. While requiring confirmation, patients may benefit from a preparatory milieu that prepares them for multiple recovery pathways; decouples the psychedelic experience from clinical outcomes; and addresses potential risks of another failed treatment.